POS0153 MACROPHAGE [11C]-DPA-713 PET-CT IMAGING TO PREDICT EARLY ANTI-TNF TREATMENT OUTCOME IN RHEUMATOID ARTHRITIS
Authors: W. Binsbergen, J. De Jongh, S. Pieplenbosch, M. Yaqub, D. Van Schaardenburg, A. Voskuyl, G. C. J. Zwezerijnen, C. J. Van der Laken
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Treatment of rheumatoid arthritis (RA) using anti-tumor necrosis factor (TNF) biologics has greatly benefited patients since their introduction, with an expected treatment response rate of up to 50-70% [1]. This however, leaves 30-50% of patients taking ineffective medication whilst being exposed to the potential side-effects of anti-TNF. Current patient care requires clinical evaluation of 3 to 6 months before effectiveness can reliably be assessed. Quantitative macrophage positron emission tomography (PET) has shown potential to predict clinical response at an early stage of treatment [2]. The new generation translocator protein (TSPO) tracer [11C]-DPA-713 has demonstrated excellent properties for imaging of arthritis by targeting synovial macrophages [2, 3]. <h3>Objectives</h3> To determine whether quantitative whole body [11C]-DPA-713 PET/CT imaging at 0-4 weeks of anti-TNF treatment in clinically active RA patients is associated with clinical response at 26 weeks. <h3>Methods</h3> Whole body [11C]-DPA-713 PET/CT scans were performed at baseline and after 4 weeks of treatment with anti-TNF in n=20 clinically active RA patients. All patients were either anti-TNF naïve or switched to an anti-TNF agent without previous primary failure to anti-TNF. Co-treatment with DMARD and/or low dose (≤ 10 mg dd) was allowed and was stable for at least 4 weeks. Clinical follow-up was conducted with the Disease Activity Score 44 (DAS44) after 26 weeks of treatment. PET/CT scans were quantitatively analyzed using in-house software. Regions of interest (ROIs) were delineated on PET/CT per individual joint in all joints evaluated using the DAS44 and CT as anatomical reference. Standardized uptake values (SUVs) normalized for body weight were calculated in these ROIs to determine quantitative tracer uptake per joint. PET outcome at baseline and 4 weeks of anti-TNF treatment was compared with the DAS44 scores at 26 weeks of treatment. <h3>Results</h3> Included patients were mostly female (70%) and aged 61.5 ± 12.8. Baseline DAS44 was 2,5 ± 1 and all demonstrated visually enhanced tracer uptake in one or more joints on PET/CT. After 26 weeks 30% showed no response, 20% moderate response and 50% good response to treatment according to EULAR response criteria. Baseline mean PET/CT scores of all joints per patient already correlated significantly with DAS44 at 26 weeks (T=0, R<sup>2</sup> = 0.547, <i>p</i> = &lt;0,001). In smaller joint clusters the highest correlation was found for the metacarpal-phalangeal joints (T=0, R<sup>2</sup> = 0.650, <i>p</i> = &lt;0.001). Furthermore, PET/CT outcomes at 4 weeks of anti-TNF treatment also had significant correlation with DAS44 at 26 weeks for those same measurements: mean score of all joints: T=4, R<sup>2</sup> = 0,530, <i>p</i> = &lt;0,001, mean score MCPs: T=4, R<sup>2</sup> = 0.728, <i>p</i> = &lt;0,001. <h3>Conclusion</h3> Quantitative whole body macrophage C-11-DPA713 PET/CT joint assessment correlated already at baseline, and also at 4 weeks of anti-TNF treatment with clinical response at 6 months of treatment. Therefore, quantitative non-invasive macrophage PET/CT shows promise for very early prediction and treatment stratification of anti-TNF in RA patients. Further studies will be focused on development of standardized and (semi-)automated PET quantification protocols to facilitate implementation in clinical trials and practice. <h3>References</h3> [1]Aletaha, D. et al., JAMA, 2018. <b>320</b>(13): p. 1360-1372. [2]Verweij, N. et al., RMD Open, 2022. <b>8</b>(1). [3]Yaqub, M. et al., Int J Mol Sci, 2020. <b>21</b>(9). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Wouter Binsbergen: None declared, Jerney de Jongh: None declared, Simone Pieplenbosch: None declared, Maqsood Yaqub: None declared, Dirkjan van Schaardenburg: None declared, Alexandre Voskuyl: None declared, Gerben C.J. Zwezerijnen: None declared, Conny J. van der Laken Consultant of: Novartis, Pfizer, Abbvie, UCB, Bristol Myers Squibb, GlaxoSmithKline, Galapagos, Grant/research support from: Novartis, Pfizer, Abbvie, UCB, Bristol Myers Squibb, GlaxoSmithKline, Galapagos.